title: T-cell help dependence of memory CD8+ T-cell expansion upon vaccinia virus challenge relies on CD40 signaling.
abstract: Due to their capacity to differentiate into long-lived memory cells, CD8(+) T cells are able to resolve subsequent infections faster than during the primary response. Among other factors, CD4(+) T cells play a crucial role during primary and secondary CD8(+) T-cell responses. However, the timing and mechanisms by which they influence CD8(+) T cells may differ in primary and secondary responses. Here, we demonstrate that during both primary and secondary vaccinia virus infection, CD4(+) T cells are necessary to promote CD8(+) T-cell responses. While CD4(+) T cells contributed to memory CD8(+) T-cell development, they were even more important during memory recall responses during challenge, as absence of CD4(+) T cells during challenge resulted in markedly decreased proliferation and increased apoptosis. T-cell help during primary and secondary responses was mediated via CD40 signaling, with DCs being an integral part of that pathway. As opposed to primary CD8(+) T-cell responses where only a combination of agonistic CD40 signaling and provision of IL-2 could substitute for T-cell help, agonistic CD40 triggering alone was sufficient to rescue memory CD8(+) T-cell responses in absence of T-cell help in the context of vaccinia virus infection.
authors.affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: Gregor
authors.initials: G
authors.lastname: Bedenikovic
authors.forename: Josh
authors.initials: J
authors.lastname: Crouse
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D019013:CD40 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D007376:Interleukin-2
keywords: CD4+ T cell; CD40-signaling; Secondary CD8+ T-cell responses; T-cell help; Vaccinia virus